Cardiac and vascular responses after monocrotaline-induced hypertrophy in rats.
In rats, monocrotaline causes pulmonary vascular damage leading to pulmonary hypertension, right ventricular hypertrophy, and eventually heart failure. This study determined the inotropic and chronotropic responses in isolated cardiac tissues from pulmonary hypertensive rats (single treatment with monocrotaline, 105 mg/kg) to noradrenaline, forskolin, EMD 57033 (calcium sensitizer), and calcium chloride. Further, vasoconstrictor responses to noradrenaline, 5-hydroxytryptamine (5-HT), and KCl were measured in isolated pulmonary artery and thoracic aortic rings. Marked right ventricular hypertrophy was evident 4 weeks after treatment; at 6 weeks, treated rats additionally showed symptoms of severe heart failure. Pulmonary hypertension led to marked increases in pulmonary artery responses to 5-HT and to decreases in positive inotropic responses in right ventricular papillary muscles to all compounds except calcium chloride. The development of heart failure maintained or increased these changes. Positive chronotropic responses were unchanged. In the right ventricle, beta1-adrenoceptor density decreased only in heart failure; beta2-adrenoceptor density was unchanged. The densities of both beta-adrenoceptor subtypes were decreased in the lungs but increased in the liver of pulmonary hypertensive rats. The functional changes in the failing human heart are similar to those in rats with monocrotaline-induced right ventricular hypertrophy. This may be a useful model to define adequate therapy in human right ventricular failure.
Brown
L
L
Department of Physiology and Pharmacology, The University of Queensland, Australia.
Miller
J
J
Dagger
A
A
Sernia
C
C
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects*; D006976:Hypertension, Pulmonary / Q000139:chemically induced; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline; D009200:Myocardial Contraction / Q000187:drug effects*; D011042:Poisons; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D013268:Stimulation, Chemical; D014661:Vasoconstriction / Q000187:drug effects*
D011042:Poisons; D011943:Receptors, Adrenergic, beta; D016686:Monocrotaline